National Institute of Mental Health (NIMH)
National Institute on Aging (NIA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute on Drug Abuse (NIDA)
National Institute of Nursing Research (NINR)
National Institute on Minority Health and Health Disparities (NIMHD)
National Center for Complementary and Integrative Health (NCCIH)

All applications to this funding opportunity announcement should fall within
the mission of the Institutes/Centers. The following NIH Offices may co-fund
applications assigned to those Institutes/Centers.

Division of Program Coordination, Planning and Strategic
Initiatives, Office of Behavioral and Social Sciences Research (OBSSR)
Office of Research on Women’s Health (ORWH)

In April 2018, the National Institutes of Health (NIH)
launched the HEAL (Helping to End Addiction Long-term) Initiative, an aggressive,
trans-agency effort to speed scientific solutions to stem the national opioid
public health crisis. In response to this initiative, the National Institute
of Mental Health (NIMH), in partnership with other NIH Institutes, proposes
research to adapt the Collaborative Care Model (referred to henceforth as
collaborative care) – a specific service delivery model for treating
mental/behavioral health conditions in primary care settings – to meet the
needs of individuals with opioid use disorders (OUDs) and co-occurring mental
health conditions. Effectiveness clinical trials are envisioned to develop,
optimize, implement, scale, and sustain collaborative models that offer
Medication Assisted Treatment for OUD alongside indicated treatment for
mental health conditions that commonly co-occur with OUD and are treatable in
primary care.

Key Dates

Posted Date

December 10, 2018

Open Date (Earliest Submission Date)

March 1, 2019

Letter of Intent Due Date(s)

March 1, 2019

Application Due Date(s)

April 1, 2019, by 5:00 PM local time of applicant
organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

No late applications will be accepted for this Funding
Opportunity Announcement.

Applicants are encouraged to apply early to allow adequate
time to make any corrections to errors found in the application during the
submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

May/June 2019

Advisory Council Review

August 2019

Earliest Start Date

October 2019

Expiration Date

April 2, 2019

Due Dates for E.O. 12372

Not Applicable

Required
Application Instructions

It is critical that applicants follow the Research (R) Instructions
in the SF424
(R&R) Application Guide, except where instructed to do otherwise (in
this FOA or in a Notice from the NIH
Guide for Grants and Contracts). Conformance to all requirements (both
in the Application Guide and the FOA) is required and strictly enforced. Applicants
must read and follow all application instructions in the Application Guide as
well as any program-specific instructions noted in Section IV. When the program-specific
instructions deviate from those in the Application Guide, follow the
program-specific instructions. Applications that do not comply with
these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and
Department of Health and Human Services partners. You must use one of these submission
options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online.

This
funding opportunity announcement (FOA) is being offered as part of the NIH’s
Helping to End Addiction Long-term (HEAL) initiative to speed scientific
solutions to the national opioid public health crisis. The NIH HEAL Initiative
will bolster research across NIH to (1) improve treatment for opioid misuse and
addiction and (2) enhance pain management. More information about the HEAL
Initiative is available at: https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative.

The current NIMH FOA will support effectiveness clinical
trials that develop, optimize, and test collaborative care models based in
primary care to furnish indicated treatment for people with opioid use
disorders (OUDs) and co-occurring mental health conditions. In these
collaborative care models, Medication Assisted Treatment (MAT) must be offered
alongside indicated treatments for other mental health conditions that commonly
co-occur with OUD (e.g., depression, anxiety, and/or PTSD).

Background

National survey data suggest around
2.1 million Americans ages 12 years and older had an opioid use disorder (OUD)
in 2016; and that, among adults who misused opioids in the prior year, 15.6%
also had a serious mental illness and 42.8% had any mental illness. OUDs are
also associated with various serious co-occurring physical health conditions,
as well as high risk of premature death via accidental overdose, other accident
mortality, and suicide (via intentional self-poisoning, as well as by other means).
In 2016, 42,000 people died from opioid overdoses in the US, which represents a
five-fold increase since 1999.

Substantial evidence documents the effectiveness of certain
medications, particularly buprenorphine and methadone, for treating OUDs, especially
when such medications are combined with behavioral health counseling and
delivered via coordinated Medication Assisted Treatment (MAT). MAT can
significantly increase rates of recovery and reduce risk of fatal and non-fatal
overdose. Despite a 2015 Practice Guideline from the American Society of
Addiction Medicine that focuses on the use of medications in the treatment of
substance use disorders involving opioid use, and a recommendation within the
CDC Prescribing Guideline that clinicians offer MAT for patients with OUD, MAT
remains underutilized. Only around one in five people with OUD receive any
specific treatment, and only a minority of those receive MAT. Even among
individuals who do receive indicated OUD treatments, effectiveness in current
usual practice is limited.

Geographic availability of clinicians who provide MAT and
other indicated OUD treatments is highly variable and is especially limited in
rural and other areas where OUD morbidity and mortality rates have risen
steeply. The Substance Abuse and Mental Health Services Administration
(SAMHSA) reports that approximately half of US counties lack even one
practicing mental/behavioral health specialty clinician. Of counties that do
have providers certified to prescribe buprenorphine for OUD, most providers
practice well under the patient caps, with 40% of certified providers not
prescribing any buprenorphine. Together, these factors identify an urgent need
for better models of care for individuals with OUD, to improve access, quality,
and clinical outcomes.

Over 80 randomized controlled trials demonstrate the
effectiveness of collaborative care for improving clinical and service delivery
outcomes among patients presenting in primary care with various common
mental/behavioral health conditions, particularly mood and anxiety disorders,
including those with co-occurring physical health problems. Collaborative care
programs have been implemented and tested in diverse health care settings,
including network and integrated systems, and private and public providers;
different practice sizes; and different patient populations, including both
insured and uninsured/safety-net populations. Compared to usual practice,
collaborative care improves mental and physical health outcomes, functioning,
and labor market outcomes; is associated with reductions in suicidality;
increases access to care and improves quality of care; reduces disparities in
quality and outcomes; and is relatively cost-effective and in some cases, is
cost-saving. As such, collaborative care holds promise as an effective,
scalable, sustainable, and readily implementable service delivery model for
people with complex needs.

In collaborative care, care is
provided to a panel of patients by a treatment team. Team members include the
primary care provider, a care manager, and a behavioral health specialty
consultant. The care manager supports the patient and the primary care provider
through a variety of treatment coordination activities. These activities
include proactive follow-up of treatment adherence, tolerance, and response,
alerting treatment team members when the patient is not improving; supporting
medication management; facilitating communication among the treatment team; and
delivering brief interventions like motivational interviewing, behavioral
activation, and problem-solving therapy. The behavioral health specialty
consultant, who has expertise and authority to prescribe medications, advises
the primary care treatment team regarding patients who present diagnostic
challenges or who are not adequately adhering, tolerating, or responding to
treatment. Such consultation can be provided in person, or via tele- or
web/video-conference to help address geographic scarcity. Teams may be
augmented to include clinicians who furnish psychotherapy or other indicated
treatments, or such treatments can be furnished via referral. Collaborative
care programs follow the principles of measurement-based care,
treatment-to-target, stepped care, and shared patient-provider decision making.
In collaborative care, new cases are identified thorough routine screening, and
patients’ progress is closely tracked using validated instruments. Treatment is
adjusted – stepped up – if patients are not improving as expected.

Evidence supporting collaborative care is strongest for
common mental disorders but is less robust for OUD and other substance use
disorders. While collaborative care trials focusing on common mental disorders
have typically included patients with co-occurring substance use disorders,
research has typically not examined effectiveness separately for those with and
without such co-occurring conditions.

This FOA will support research to address unanswered
questions regarding the adaptation, effectiveness, and implementation of
collaborative care for individuals with OUD and co-occurring mental health
conditions. This research will complement studies conducted within OUD
specialty care clinics by testing integrated treatment models appropriate for
diverse primary care settings, where many patients with OUDs and mental health
conditions already seek care, and that are more plausibly available in areas
where behavioral health specialty providers are - and are likely to remain -
scarce.

The anticipated effectiveness trials will channel the
efforts of the scientific community to develop and implement pragmatic,
effective, scalable, and sustainable solutions to the formidable public health
challenges of OUD, which affect the lives and welfare of millions of Americans.

Public Law 115-141, the Consolidated Appropriations Act of 2018 (signed March 23, 2018) includes a requirement that grantees from for-profit applicant organizations must provide a 50% match and/or in-kind contribution of all federally awarded dollars under the grant award (direct costs, as well as facilities and administrative costs) for research related to opioid addiction, development of opioid alternatives, pain management and addiction treatment.

Matching Requirement: A grantee from a for-profit organization funded under this funding opportunity announcement must match funds or provide documented in-kind contributions at a rate of not less than 50% of the total-Federally awarded amount, as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018.The applicant will be required to demonstrate that matching funds and/or in-kind contributions are committed or available at the time of, and for the duration of, the award. Applications must identify the source and amount of funds proposed to meet the matching requirement and how the value for in-kind contributions was determined. All matching funds and/or in-kind contributions must be used for the portion of allowable project costs not paid by Federal funds under the grant award. NIH will not be the recipient, nor serve as a pass-through entity, of any such matching funds and/or in-kind contributions required under this announcement. See 45 CFR 75.306 for additional details.

Research Objectives

NIH is interested in supporting effectiveness trials that
develop, optimize, and test collaborative care models based in primary care to
furnish indicated treatment for people with OUD and co-occurring mental health
conditions. The collaborative care model must include MAT for OUD--specifically
including indicated medications such as buprenorphine and/or methadone--as a
component of care. The comparative effectiveness trials should be designed to
support rapid implementation, scalability, and sustainability of collaborative
care approaches, should findings be positive.

Two categories of patients would be the primary foci for
enhancing quality of care and improving clinical outcomes via the collaborative
care model:

Individuals presenting or referred to primary care who are
identified with an OUD and one or more co-occurring mental health conditions
and who, based on shared patient-provider decision-making, choose to receive
treatment for these conditions in primary care;

Individuals with an OUD and one or more co-occurring mental
health condition presenting to a hospital emergency department or other acute
care setting with non-fatal overdose, intentional self-harm, or other
OUD-related emergent risk, and who prefer to receive follow-up outpatient care
after discharge in primary care (including because they lack access to
specialty care).

To meet the needs of people with OUD and mental health
conditions, applicants should seek to answer these important primary research
questions:

How can routine screening practices in primary care and as part
of collaborative care be improved to identify new patients with OUD and mental
health conditions?

When compared to standard care, how much does collaborative care
improve access to and engagement with evidence-based services? That is, what is
the reach of collaborative care into the target population?

How can collaborative care be optimized to introduce MAT to
existing primary care practices already offering collaborative care for
depression, anxiety, or other mental health conditions?

How can collaborative care for MAT and mental health conditions
be introduced to primary care practices not providing collaborative care?

What patient, provider, and health system-level strategies are
most effective to implement, bring to scale, and sustain collaborative care in
diverse primary care practice settings for people with OUD and mental health
conditions?

NIH is particularly interested in clinical trial designs
which can secondarily answer the following questions:

Does treatment of mental health conditions also improve outcomes
for people with OUDs?

What are the clinical and treatment engagement tradeoffs
associated with sequencing mental health treatment ahead of treatment for OUD?
How can designs that study treatment sequencing inform clinical practice
guidelines for co-occurring disorders and inform shared patient-provider
decision making during initial treatment planning?

Can improved collaborative care for OUD and mental disorders be
considered “primary prevention” for acute overdose, suicide behaviors, and/or
accidental death - catastrophic outcomes for which individuals with OUD have
very elevated risk?

Can collaborative care be part of a care pathway for individuals
with OUD who have been identified via presentation to a hospital emergency
department or other acute care setting with non-fatal overdose or suicide
attempt? And if so, under what conditions would this pathway be reasonable and
effective in the context of other alternatives (e.g., immediate inpatient
hospitalization if beds are available, emergency department boarding followed
by inpatient hospitalization, telehealth consultation with a behavioral health
specialist, warm handoff to an outpatient behavioral health specialist, usual
care discharge home)?

Given the public health urgency to furnish high value
services that are effective, scalable, and sustainable in real-world practice,
NIH is additionally interested in answering these questions:

How well do existing financing models support the implementation
of collaborative care models for treating individuals with OUD and co-occurring
mental health conditions? What are the major barriers to wider implementation
of collaborative care for these purposes, and practical options for addressing
them?

What are the best strategies to ensure collaborative care models
are implemented, adopted, scaled, and sustained in routine practice, to include
rural and Native American settings, and other settings of high need which may
be under resourced?

Institute
Interests

NCCIH

The mission of NCCIH is to define, through rigorous scientific
investigation, the usefulness and safety of complementary and integrative
health interventions and their roles in improving health and health
care. in the context of this FOA, NCCIH is interested in studies that will
evaluate the impact of adding evidence-based complementary approaches for
mental health conditions that are commonly co-occurring with OUD, such as mood
disorders, anxiety, or sleep disorders, to determine if they have a measurable
impact on improving OUD outcomes. Applicants are encouraged to discuss
applications the NCCIH contact listed in Section
VII. Agency Contacts.

NIAAA

Given the substantial co-occurrence of OUD, mental health issues,
and alcohol use disorder, service delivery models that emphasize integration of
care for behavioral health in general medical settings are of particular
importance. In the context of this FOA, NIAAA is interested in studies
that will assess whether and how the benefits of collaborative care models
extend beyond patients’ OUD and mental health outcomes to other co-occurring
behavioral health conditions, particularly heavy drinking and alcohol use
disorder. In addition, NIAAA encourages studies that will examine the influence
of alcohol drinking history and current drinking on the efficacy of
collaborative care models as applied to OUD and co-occurring mental health
conditions. Applicants are encouraged to discuss applications with the
NIAAA contact listed in Section
VII. Agency Contacts.

OBSSR

Although OBSSR does not accept assignment of applications or
manage awards that are funded through this announcement, OBSSR does encourage
applications relevant to the OBSSR mission and may provide co-funding support
to ICs that do manage the awards. OBSSR is specifically interested in
studies that apply evidence-based approaches for behavioral change (e.g.,
provider prescribing practices, adherence to treatment and management
recommendations for both the practitioner and patients, provider/patient
communications, resilience and other topics) to improve outcomes within the
collaborative care model.

ORWH

The Office of Research on Women’s Health (ORWH) is part of the
Office of the Director of NIH and works in partnership with the 27 NIH
Institutes and Centers to ensure that women's health research is part of the
scientific framework at the NIH, and throughout the scientific community. In
general, ORWH is interested in research that considers the influence of sex and
gender on health and disease, and the total health of women across the full
spectrum of research. ORWH encourages interdisciplinary approaches and would be
interested in partnering to support research that examines ways to integrate
evidence-based practices, interventions, and policies into practice settings to
improve the health of women. The Trans-NIH Strategic Plan for the Health
of Women covering FY 2019 - 2023 is available on the ORWH website (https://orwh.od.nih.gov) for additional
guidance.

Scale and Scope of Research Covered Under This
Announcement

This FOA is intended to support trials that are
statistically powered to provide a definitive answer regarding the
effectiveness of collaborative care for people with OUD and co-occurring mental
health conditions in comparison to usual care practices or alternative
intervention/services approaches. The study should also be designed to address
hypotheses regarding predictors and moderators of effectiveness and questions
regarding the action of mediators and mechanisms that underlie improvements to
service delivery, implementation, scalability, and sustainability of
collaborative care.

This FOA
is intended to only fund strategies that optimize and test collaborative care
for OUD and co-occurring mental health conditions. This FOA is not
intended to test other models of integration (e.g., co-location of a behavioral
health provider into primary care in the absence other elements like care
management services or application of measurement-based care). It is also not
intended to support other efforts like the development of treatment guidelines
and education of primary care providers, in the absence of collaborative care.

NIH envisions an intervention arm that integrates both MAT for OUDs and
treatment for indicated mental health conditions within a collaborative care
model of service delivery. Here, the behavioral health consultant must also
advise directly on MAT services (or ensure regular expert consultation is
available to the care team about MAT). Workflows, decision support tools,
principles of measurement-based care and treatment-to-target, strategies to
engage patients in care, etc. that are used in collaborative care for patients
with mental health conditions should also be adapted (if necessary) and used as
part of MAT services that are integrated with collaborative care.

Study sites should be representative and in areas of high
need. The proposed projects should be multi-site and potentially include entire
states like New Hampshire, West Virginia, New Mexico, Kentucky, or Ohio.

Projects must specify the patient outcomes that will be the
focus of treatment; provide detailed rationale for the choice of outcomes; and
describe valid and standardized methods for how those outcomes will be
measured. Wherever possible, projects should utilize existing validated,
standardized instruments of patient outcomes, which are available for many
mental disorders and for functioning.

Given the urgency for rapid implementation of pragmatic and
effective interventions to stem the opioid crisis, projects must demonstrate a
deployment-focused model of design and testing. That is, studies should take
into account key characteristics of the settings, providers, and intervention
elements (e.g., training, supervision, infrastructure, and capacity to pursue
measurement-based care) and factors related to implementation (reach,
effectiveness, adoption, and maintenance). Designs should be pragmatic, and
procedures and infrastructure unique to research (e.g., recruitment and
follow-up strategies) should have minimal impact on clinical care and should
not confound the interpretation of intervention effects or the generalizability
of findings to non-research settings. A deployment focus is crucial to ensure
that clinical trials that test collaborative care for people with OUDs and
co-occurring mental health conditions have sufficient external validity to
support broad implementation of evidence-based practices outside of a clinical
trial context.

NIH will give priority to studies that leverage existing
equities (e.g., practice networks, clinical trial networks, research-practice
partnerships) rather than those that need to create research and clinical
infrastructure de novo.
Collaborations between academic researchers and clinical or community practice
partners or networks are expected. When possible, studies should capitalize on
existing infrastructure. Examples include practice-based research networks such
as the NIMH-sponsored Mental Health Research Network (MHRN), the NIDA supported
Clinical Trials Network, the NCATS Trial Innovations Network, the AHRQ Clinical
Directors Network, and other clinical infrastructure (e.g., federal qualified
health centers, rural health clinics, other integrated care settings supported
by federal partners like HRSA or SAMHSA. Other examples may include leveraging
electronic medical records, administrative data bases, and patient registries
to increase the efficiency of participant recruitment (i.e., more rapid
identification and enrollment) and to facilitate the collection of moderator
data (e.g., patient, provider, and setting characteristics), longer-term
follow-up data, and broader, stakeholder-relevant outcomes (e.g., mental health
and general health care utilization, value and efficiency of intervention
approaches).

Effective prevention, treatment, and management of OUD and
mental health conditions have the potential to reduce morbidity and mortality
associated with intentional injury (i.e., suicide attempts and deaths,
see: www.suicide-research-agenda.org)
and accidental overdose. Lack of attention to the assessment of these
outcomes has limited our understanding regarding the degree to which MAT and
indicated mental health treatment might offer prophylaxis. Accordingly,
NIMH encourages effectiveness research that includes assessment of suicidal
behavior to advance understanding of how effective prevention and treatment of
mental disorders might impact suicide-relevant outcomes.

This funding announcement is intended to invite single
applications that will use subcontracts to fund research being conducted at
multiple clinical sites and/or fund investigators at multiple research
institutions.

This RFA is not intended to support the development and testing of novel treatment modalities
for the conditions being targeted here, i.e., new psychotherapies, medications,
devices, or other treatments that are not yet indicated for OUD or relevant
mental health conditions. Rather, this RFA is intended to support innovations in the delivery of existing efficacious
treatment, when integrated as part of an optimized collaborative care model.
Similarly, this RFA is also not intended to support the development and testing
of new screening or patient outcome instruments. Wherever feasible and
appropriate, projects should utilize existing validated and standardized
instruments to screen for OUD and other substance use, as well as for common
mental health conditions, as well as existing validated and standardized
instruments to assess patient outcomes related to OUD, specific mental health
conditions, functioning, and other relevant patient outcomes.

Examples
of studies that are considered low priority to this FOA include the following:

Studies that do not include these core elements of the
collaborative care model to be tested:1) A prepared primary care practice
(e.g., routine screening for indicated conditions; real-time availability and
use of a disease registry for measurement-based care and treat-to-target
practices for a panel of patients); 2) Care management services (in-person
and/or via telehealth); 3) A behavioral health consultant with prescription
privileges, with collaborative care expertise and with MAT expertise (if the
behavioral health consultant does not have the prerequisite expertise,
applicants must provide a plan for how that expertise will be obtained and
provided to the care team); 4) Integration of MAT for OUD within the
collaborative care model; 5) Indicated treatment for mental health conditions
commonly seen in primary care settings (e.g., depression, anxiety, and/or
PTSD); and 6) Shared patient-provider decision making.

Projects that do not demonstrate a deployment-focused model of
design and testing. That is, studies that do not take into account key
characteristics of the settings, providers, and intervention elements.

Designs that are not pragmatic, and/or do not have procedures and
infrastructure unique to research (e.g., recruitment and follow-up strategies)
that have minimal impact on clinical care and minimal impact on trial results.

Projects that do not explicitly inform understanding regarding
whether collaborative care engages putative change mechanisms (i.e., targets) related to
service delivery that are presumed to account for improved outcomes.

Cooperative Agreement: A support mechanism used when there
will be substantial Federal scientific or programmatic involvement.
Substantial involvement means that, after award, NIH scientific or program
staff will assist, guide, coordinate, or participate in project activities. See
Section VI.2 for additional information about the substantial involvement for
this FOA.

Application Types Allowed

New

The OER
Glossary and the SF424 (R&R) Application Guide provide details on
these application types.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are
not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible
to apply.
Foreign components, as defined in
the NIH Grants Policy Statement, are allowed.

Required
Registrations

Applicant
Organizations

Applicant organizations must complete and maintain the
following registrations as described in the SF 424 (R&R) Application Guide
to be eligible to apply for or receive an award. All registrations must be
completed prior to the application being submitted. Registration can take 6
weeks or more, so applicants should begin the registration process as soon as
possible. The NIH
Policy on Late Submission of Grant Applications states that failure to
complete registrations in advance of a due date is not a valid reason for a
late submission.

Dun and Bradstreet
Universal Numbering System (DUNS) - All registrations require that
applicants be issued a DUNS number. After obtaining a DUNS number, applicants
can begin both SAM and eRA Commons registrations. The same DUNS number must be
used for all registrations, as well as on the grant application.

System for Award Management (SAM)–
Applicants must complete and maintain an active registration, which requires renewal at least
annually. The renewal process may require as much time as the
initial registration. SAM registration includes the assignment of a Commercial
and Government Entity (CAGE) Code for domestic organizations which have not
already been assigned a CAGE Code.

eRA Commons - Applicants
must have an active DUNS number to register in eRA Commons. Organizations can
register with the eRA Commons as they are working through their SAM or
Grants.gov registration, but all registrations must be in place by time of
submission. eRA Commons requires organizations to identify at least one Signing
Official (SO) and at least one Program Director/Principal Investigator (PD/PI)
account in order to submit an application.

Grants.gov – Applicants
must have an active DUNS number and SAM registration in order to complete the
Grants.gov registration.

Program
Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.
PD(s)/PI(s) should work with their organizational officials to either
create a new account or to affiliate their existing account with the applicant
organization in eRA Commons. If the PD/PI is also the organizational Signing Official,
they must have two distinct eRA Commons accounts, one for each role. Obtaining
an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal
Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

For grantees from a for-profit organization, this FOA does require cost sharing, as defined in the NIH Grants Policy Statement. More information on cost matching requirements is in Section IV.2 R&R or Modular Budget

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping
applications under review at the same time. This means that the NIH will
not accept:

A new (A0) application that is submitted before issuance of the
summary statement from the review of an overlapping new (A0) or resubmission
(A1) application.

A resubmission (A1) application that is submitted before issuance
of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another
application pending appeal of initial peer review (see NOT-OD-11-101).

Section IV. Application and Submission Information

1. Requesting an
Application Package

The application forms package specific to this opportunity
must be accessed through ASSIST, Grants.gov Workspace or an institutional
system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are
available in Part 1 of this
FOA. See your administrative office for instructions if you plan to use an
institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Research (R) Instructions
in the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

Letter of Intent

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows IC staff to estimate the potential review workload and
plan the review.

By the date listed in Part 1. Overview
Information, prospective applicants are asked to submit a letter of intent
that includes the following information:

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in
the SF424 (R&R) Application Guide and should be used for preparing an
application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide
must be followed with the following additional instructions:

Key Personnel should document their expertise conducting
collaborative care clinical trials; their expertise delivering or researching
MAT; their familiarity with state and federal regulations pertaining to MAT
delivery; their knowledge about Medicaid, Medicare, and commercial insurance
benefit packages associated with collaborative care and MAT; their expertise
implementing collaborative care programs in diverse geographic areas; their
expertise collecting and integrating de-identified, person-level data gathered
across multiple clinics and using standardized data to improve the quality of
mental health services and individual patient outcomes; and their success
conducting services and/or intervention research with individuals who have
complex needs, including success in identifying and recruiting such
participants into research studies.

Applicants should document their experience working in
community practice primary care and other relevant settings (e.g., the
emergency department) and with administrators and clinic leaders to integrate
standardized assessment methods and health information technology into routine
clinical care and in establishing collaborations across diverse mental health
care stakeholders, such as patients, families, clinicians, researchers,
administrators and payors to create organizational and/or cultural change in
mental healthcare delivery. Applications should include information
demonstrating the investigator’s or co-investigator’s capacity to identify,
recruit, randomize, and retain individuals who have OUDs and mental health
conditions in numbers sufficient to support an adequately powered randomized
clinical trial. Investigators should also demonstrate experience in clinical
trials management.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide
must be followed with the following additional instructions:

Budget
Justification related to for-profit entities: All requests
from for-profit entities must document the matching (non-Federal) component and
the federal (non-matching) component in the total project budget. That is, the
requested budget plus the cost-matching budget must be detailed in tabular
format to document the cost-matching (non-Federal) component and the federal
(non-cost matching) component. The amount of matching is subject to adjustment
based on total allowable costs incurred. All costs and contributions used
to satisfy the matching requirement must be documented by the recipient, including
how the value for in-kind contributions was determined, and are subject to
audit. The cost matching requirement is not negotiable for for-profit
organizations.

Cost Matching Requirement for For-profit Applicants

Cost matching or documented in-kind contributions is required for for-profit organizations responding to this FOA. The for-profit awardee is required to match funds or provide at least a 50% matching of funds or documented in-kind contributions at a rate of not less than 50% of the for the total-Federally awarded amount (direct costs, as well as facilities and administrative costs), as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018.
Federal funds may not be used as a source of matching funds. Generally, cost matching requirements may not be met from the following sources:
a) Costs borne by another Federal grant or sub award;
b) Costs or contributions toward cost sharing on another Federal grant, a Federal procurement contract, or any other award of Federal funds;
c) Cost of services or property financed by income earned by contractors under a contract from the recipient (or sub recipient);
(d) Program income; and
(e) Patient incentives.
The for-profit organization will be required to demonstrate that matching funds and/or in-kind contributions are committed or available at the time of, and for the duration of, the award. Applicants must submit budgets that clearly document the total costs, the source and amount of matching funds, and how valuation was determined in the case of in-kind contributions, as well as the Federal and Institutional (non-Federal) components of the budget. All matching funds and/or in-kind contributions must be used for the portion of allowable project costs not paid by Federal funds under the grant award. NIH will not be the recipient, nor serve as a pass-through entity, of any such matching funds and/or in-kind contributions required under this announcement. See 45 CFR 75.306 for additional details.Budget Justification: All for-profit applicants must document the matching (non-Federal) component and the federal (non-matching) component in the total project budget. That is, the requested budget plus the cost-matching budget must be detailed in tabular format to document the cost-matching (non-Federal) component and the federal (non-cost matching) component. The amount of matching is subject to adjustment based on total allowable costs incurred. All costs and contributions used to satisfy the matching requirement must be documented by the recipient, including how the value for in-kind contributions was determined, and are subject to audit. The cost matching requirement is not negotiable for for-profit organizations.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Research
Strategy

Applications must describe a feasible mechanism for
scientific integration of research procedures and overall managerial and
administrative responsibilities across participating clinic sites. The common
research protocol must specify mechanisms for cross-site coordination of
clinical assessment, data collection, training and supervision for the care
team, fidelity monitoring, and database management to assure reliability and
quality control. The research grant application is expected to include central
data coordination and statistical analysis support for the overall project. In
addition, the Research Strategy should include the following information.

Describe the process for establishing and convening a
Steering Committee, including the composition, roles/responsibilities, and
schedule for convening regular and ad hoc steering committee meetings

Significance

Explain the importance of the problem or critical barrier to
progress that the proposed project addresses. Describe the scientific premise
for the proposed project, including consideration of the strengths and
weaknesses of published research or preliminary data crucial to the support of
your application. Explain how the proposed project will improve scientific
knowledge, technical capability, and/or clinical practice in one or more broad
fields.

Indicate how scientific knowledge, technical capability,
clinical practice and/or health policy for the treatment and management of OUD
and co-occurring mental health conditions could be improved if the aims of the
project are achieved. Indicate how successful completion of the project aims
could change the concepts, methods, technologies, treatments, and services,
that drive care for individuals with OUDs and co-occurring mental health conditions.

Justify the practical impact of the collaborative care
intervention to be tested in terms of the estimated hypothesized effect size
compared with already available approaches. Address the potential impact of the
collaborative care intervention in terms of both (1) the empirical basis for
the anticipated effect size (e.g., citing data from prior collaborative care
trials, trials testing MAT, and/or trials of indicated treatments for mental
health conditions in primary care settings), and (2) the clinical
meaningfulness of the anticipated increment in effects compared to existing
approaches.

As appropriate, address the degree to which the study can
answer questions of secondary interest to NIH. For example:

Describe the importance and implications of an evidence-based
approach to treatment sequencing for people with co-occurring OUD and MH
disorders.

Address the degree to which the collaborative care model can be
adoptable, scalable, and sustainable in routine practice settings, given
typically available resources (e.g., trained, skilled providers), typical
service structures (including existing financing models), and typical service
use patterns. Address how the collaborative care model can increase both the
reach and effectiveness of care for people with OUDs and co-occurring mental
health conditions, when compared to usual care practices.

Innovation

Explain how the application challenges and seeks to shift
current research or clinical practice paradigms. Describe any novel theoretical
concepts, approaches or methodologies, instrumentation or interventions to be
developed or used, and any advantage over existing methodologies,
instrumentation, or interventions. Explain any refinements, improvements, or
new applications of theoretical concepts, approaches or methodologies,
instrumentation, or interventions.

Propose innovations in care integration, including:

Innovations in clinical workflows, recommendations for treatment
sequencing, identification and management of patients at high risk for overdose
or suicide, quality of care metrics, and integration of mental health treatment
and MAT within collaborative care.

Innovations to improve the care pathway for people with OUD and
mental health conditions into collaborative care from other settings like
emergency departments, specialty care outpatient treatment programs (OTPs),
other community settings, or other primary care practices that are ill-equipped
to treat individuals with OUD and mental health conditions.

Innovative strategies to rapidly increase intensity of services
to address the short-term needs of people in crisis when such services do not
exist.

Highlight how innovative research strategies and
design/analytic elements (e.g., adaptive sequential randomization, equipoise
stratification) are incorporated, as appropriate, in order to enhance the
study's potential for yielding practice-relevant information.

Responsive applications will include innovations in
workforce development, such as innovations in telehealth services, training and
supervision models, and/or maximizing functions of non-physician providers with
prescription privileges (e.g., NPs, PAs, and psychologists) to increase access
to services and reach of collaborative care in areas of highest need and to
inform future prescribing guidelines and rules for psychotropic medications and
buprenorphine.

Approach

Describe the overall strategy, methodology, and analyses to
be used to accomplish the specific aims of the project. Describe the
experimental design and methods proposed and how they will achieve robust and
unbiased results. Unless addressed separately in the Resource Sharing Plan,
include how the data will be collected, analyzed, and interpreted, as well as
any resource sharing plans as appropriate. Discuss potential problems,
alternative strategies, and benchmarks for success anticipated to achieve the
aims. If the project is in the early stages of development, describe any
strategy to establish feasibility, and address the management of any high risk
aspects of the proposed work.

Provide a brief overview of the target population for whom
existing services are inadequate and the settings where the collaborative care
is to be tested.

Discuss barriers and facilitators associated with
collaborative care implementation, scalability, and sustainment at the sites
where the study is to be conducted and how these factors might affect
generalizability of research findings to other primary care practices.

The approach must detail how projects will use a deployment-focused model of design and testing.
That is, studies should take into account key characteristics of the settings,
providers, and intervention elements (e.g., training, supervision,
infrastructure, and capacity to pursue measurement-based care) and factors
related to implementation (reach, effectiveness, adoption, and maintenance).
Designs should be pragmatic, and procedures and infrastructure unique to
research (e.g., recruitment and follow-up strategies) should have minimal
impact on clinical care and minimal impact on trial results. The approach
should describe how the collaborative care model to be tested has external and
face validity and how it can be feasibly delivered outside of a clinical trial
context, should it be effective. Elements of a deployment focused model include
the following:

Study samples that are representative of community practice
populations; study settings that are diverse and representative; and
interventions, screening instruments, and decision support tools that are
feasibly integrated into provider workflows, that are evidence supported, and
that can be scaled and sustained.

Assessment and/or testing of patient-, provider- and clinic-level
factors that might impact implementation, along with corresponding analyses
that will be used to examine whether/how these factors impact adoption,
scalability, sustainability, and patient outcomes, especially in settings and
locations of highest need.

Assessment plans that describe the assessment of suicidal
behavior and related outcomes using strategies that can facilitate integration
and sharing of data (e.g., see NOT-MH-15-009 and https://www.phenxtoolkit.org/ for constructs and corresponding assessment strategies), as appropriate, or
provide a rationale for excluding such measures if they are not included. Accordingly,
plans should provide the rationale for the selection of suicide-related
constructs and corresponding assessment instruments (e.g., measures of
ideation, attempts), the time periods assessed (e.g., lifetime history,
current), and the assessment schedule for administration (e.g., baseline,
during intervention, post-intervention, follow up), considering the nature of
the target population, participant burden, etc. Plans should also address
provisions for clinical management when suicidal behavior is reported. In
situations where it is not appropriate or feasible to include assessment of
suicide outcomes due to the nature of the intervention (e.g., services
interventions that target provider behavior or systems-level factors), the
target population (e.g., very young children), or unique issues related to
participant burden or safety/monitoring concerns, the application should
provide an appropriate justification for excluding these assessments.

Patient-related clinical services that are supported through
existing billing and financing mechanisms. In the event that study-related
interventions and services cannot be supported through existing mechanisms, a
justification should be provided.

Projects that leverage existing research practice partnerships
and clinical infrastructure to 1) capitalize on existing research
infrastructure whenever possible; (2) create efficiencies such that research
dollars do not support clinical infrastructure that is unsustainable upon trial
completion; and 3) ensure key research questions are highly relevant to the
practice community and findings from the study will be used to change current
practice. If applicants choose not to leverage partnerships and equities,
applicants must provide a detailed justification. Examples include
practice-based research networks like the NIMH-supported Mental Health Research Network and the
NCATS leveraged and Agency for Healthcare Research and Quality-funded Clinical Directors Network and the Rockefeller Practice Based Research
Network; other clinical trials networks like NIDA’s Clinical
Trials Network and the NCATS Trial
Innovation Network; care platforms funded by other federal agencies like
the Substance Abuse and Mental Health Services Administration the Health
Resources & Services Administration) with various community primary care
practices (e.g., Federally Qualified Health Centers, designated Rural Health
Clinics, other rural practices, integrated healthcare systems) and possibly
other healthcare settings like emergency departments.

Sites that are representative and in areas of high need. The
proposed projects should be multi-site, in areas where OUD mortality has risen
particularly steeply, and cover geographic areas the size of entire states.

Design considerations that disambiguate outcomes associated with
study participation (e.g., patient completes follow-up assessments as reported
in a CONSORT) from engagement with broad collaborative care services (e.g.,
patient is responsive to care manager outreach calls), and from individual
treatment elements delivered as part of collaborative care (e.g., patient takes
buprenorphine as prescribed and attends regular counseling sessions as part of
MAT).

Study designs that are pragmatic and that control for and/or
minimize the impact of research personnel or procedures on study outcomes.

Applicants should propose the comparison group(s) that allow
for meaningful comparisons, in light of a robust evidence base that supports
the widespread implementation of collaborative care. Describe how findings will
be interpretable and inform practice if the outcomes are positive, if outcomes
are negative, and if there is heterogeneity in the directionality of outcomes?

Applicants should provide adequate detail about the
collaborative care model(s) to be tested and the comparator(s). Required
elements of the collaborative care model to be tested must include the
following:

1)
A prepared primary care practice (e.g., routine screening for indicated conditions;
real-time availability and use of a disease registry for measurement-based care
and treat-to-target practices for a panel of patients);

2) Care management services (in-person and/or via
telehealth);

3) A behavioral health consultant with prescription
privileges, with collaborative care expertise and with MAT expertise (if the
behavioral health consultant does not have the prerequisite expertise,
applicants must provide a plan for how that expertise will be obtained and
provided to the care team);

Elements of MAT and its integration with collaborative care
should be described. This description could include the care processes,
medication type and dosing, and integration with other elements of
collaborative care during the three phases of MAT (e.g., induction,
stabilization, and maintenance).

Projects must specify the patient
outcomes that will be the focus of treatment; provide detailed rationale for
the choice of outcomes; and describe valid and standardized methods for how
those outcomes will be measured. Wherever possible, projects should utilize
existing validated, standardized instruments of patient outcomes, which are
available for many mental disorders and for functioning.

Consistent with the NIMH experimental therapeutics approach,
(http://www.nimh.nih.gov/about/director/2012/experimental-medicine.shtml),
these clinical trials will test the effectiveness of collaborative care for
people with OUD and co-occurring mental health conditions on primary outcomes
of interest, but should also explicitly inform understanding regarding whether
collaborative care engages putative change mechanisms (i.e. targets) related
to service delivery that are presumed to account for improved outcomes. (see NIMH
web page on Clinical Trials). The results of these trials will advance
knowledge regarding change mechanisms and have utility regardless of trial
outcomes (e.g., in the event of negative results, information about whether the
intervention was successful at engaging its targets can facilitate
interpretation).

Applicants should detail the plan to explicitly address whether
the intervention engages the mechanisms that are presumed to underlie the
effects of collaborative care as a service delivery model (e.g., the mechanism
that account for changes in service delivery, public health outcomes or changes
in the effectiveness of the implementation strategy) and include the following:
(1) a conceptual framework that clearly identifies the target(s)/mechanism(s)
and the empirical evidence linking the target(s)/mechanism(s) to the clinical
symptoms, functional deficits, or patient-, provider- or system-level
behaviors/processes that the intervention seeks to improve; (2) plans for
assessing engagement of the target(s)/mechanism(s) using valid measures that
are as direct, efficient, and objective as is feasible in the effectiveness
context, including the specific measures, the assessment schedule, and the
justification for the assessment strategy (e.g., evidence regarding the
validity and feasibility of the proposed measures in the effectiveness
context); and (3) a statistical analysis plan for data analyses that will be
used to examine whether the intervention engages the target(s) and whether
intervention-induced changes in the target(s) are associated with clinical
benefit (i.e., mediation).

Applicants should not necessarily specify the conceptual basis, assessment plan, and analytic
strategy, as detailed above, for the target(s)/mechanism(s) corresponding to each component of
collaborative care. Instead, applicants should do so only for service delivery
or implementation-oriented change mechanisms believed to be crucial ingredients
to effective collaborative care delivery. In this way, future adaptions of
collaborative care for the target population might retain those key ingredients
deemed effective and shed those elements deemed non-essential.

Valid and reliable measures of change in the hypothesized
target(s)/mechanism(s) will provide useful information about key change
mechanisms that account for intervention effects. NIMH encourages the use of
measures that are as direct and objective as is feasible in clinical practice
setting, including valid measures of the construct that extend beyond
self-reports and other subjective measures (e.g., data extracted from EHRs) and
span more than one level of assessment, if possible and appropriate.

If applicable, describe how the project will address
questions of secondary interest to NIH such as whether treating mental health
conditions will improve OUD-related outcomes.

Letters of Support

For-profit applicants must include a letter(s) of support confirming that the required secured cost matching (cash; in-kind commitments such as salary, consultant costs, equipment) is available and confirm that the essential personnel have the authority within the organization to allocate resources.

Resource
Sharing Plan: Individuals are required to comply with the
instructions for the Resource Sharing Plans as provided in the SF424 (R&R)
Application Guide, with the following modification:

All applications, regardless of the amount of direct costs
requested for any one year, should address a Data Sharing Plan.

In order to facilitate the goal of advancing research
through widespread data sharing among researchers, investigators funded under
this FOA are expected to share those data via the National Database for
Clinical Trials related to Mental Illness (NDCT; http://ndct.nimh.nih.gov/; see NOT-MH-14-015 and NOT-MH-15-012).
Established by the NIH, NDCT is a secure informatics platform for scientific
collaboration and data-sharing that enables the effective communication of detailed
research data, tools, and supporting documentation. NDCT links data across
research projects through its Global Unique Identifier (GUID) and Data
Dictionary technology. Investigators funded under this FOA are expected to use
these technologies to submit data to NDCT.

To accomplish this objective, it will be important to
formulate a) an enrollment strategy that will obtain the information necessary
to generate a GUID for each participant, and b) a budget strategy that will
cover the costs of data submission. The NDCT web site provides two tools to
help investigators develop appropriate strategies: 1) the NDCT Budgeting
Spreadsheet http://ndct.nimh.nih.gov/preplanning/budget - a customizable Excel worksheet that includes tasks and hours for the Program
Director/Principal Investigator and Data Manager to budget for data sharing;
and 2) plain language text to be considered in your informed consent http://ndct.nimh.nih.gov/preplanning/informed-consent.
Investigators are expected to certify the quality of all data generated by
grants funded under this FOA prior to submission to NDCT and review their data
for accuracy after submission. Submission of descriptive/raw data is expected
semi-annually (every January 15 and July 15); submission of all other data is
expected at the time of publication, or prior to the end of the grant,
whichever occurs first (see Data Sharing Expectation http://ndct.nimh.nih.gov/preplanning/#tab-1 for more information); Investigators are expected to share results, positive
and negative, specific to the cohorts and outcome measures studied by using the
Study functionality(see http://ndct.nimh.nih.gov/results).
The NDCT Data Sharing Plan is available for review on the NDCT web site (http://ndct.nimh.nih.gov/wp-content/uploads/NDCT_Data_Sharing_Policy_20141002.pdf).
NDCT staff will work with investigators to help them submit data types not yet
defined in the NDCT Data Dictionary http://ndct.nimh.nih.gov/submit/data-dictionary

Appendix:

Only limited Appendix materials are allowed. Follow all
instructions for the Appendix as described in the SF424 (R&R) Application
Guide.

PHS Human Subjects and Clinical Trials Information

When involving NIH-defined human subjects research, clinical
research, and/or clinical trials (and when applicable, clinical trials research
experience) follow all instructions for the PHS Human Subjects and Clinical
Trials Information form in the SF424 (R&R) Application Guide, with the
following additional instructions:

If you answered “Yes” to the question “Are Human Subjects
Involved?” on the R&R Other Project Information form, you must include at
least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials
Information form or Delayed
Onset Study record.

Study
Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide
must be followed with the following additional instructions:

Applications should include plans for critically evaluating
and revising these milestones on a regular basis

Section 3 - Protection and Monitoring Plans

3.5
Overall Structure of the Study Team

Provide a management plan that details how the PD(s)/PI(s)
will manage the proposed project, who will oversee the day-to-day clinical and
research activities associated with the project. This plan should include how
the study team will support achievement of the aims and milestones.

Section 5 - Other Clinical Trial-related Attachments

5.1
Other Clinical Trial-related Attachments

Applicants must upload the attachments for Intervention
Manual/Materials as separate files, as applicable. Applicants must use the
"Intervention Manual/Materials", appended with 1, 2, 3, etc. as
needed, to name these other attachments files.

As appropriate, this may include screenshots of mobile
interventions, technological specifications, training manuals or treatment
algorithms.

Delayed
Onset Study

Note: Delayed
onset does NOT apply to a study that can be described but will not start
immediately (i.e., delayed start).

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide
must be followed.

3. Unique Entity Identifier
and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the
requirement for obtaining a unique entity identifier and for completing and maintaining
active registrations in System for Award Management (SAM), NATO Commercial and
Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to
submit applications before the due date to ensure they have time to make any
application corrections that might be necessary for successful submission. When
a submission date falls on a weekend or Federal
holiday, the application deadline is automatically extended to the next
business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants
across all Federal agencies). Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants
administration. NIH and Grants.gov systems check the application against many
of the application instructions upon submission. Errors must be corrected and a
changed/corrected application must be submitted to Grants.gov on or before the application
due date and time. If a Changed/Corrected application is submitted after the
deadline, the application will be considered late. Applications that miss the
due date and time are subjected to the NIH Policy on Late Application
Submission.

Applicants
are responsible for viewing their application before the due date in the eRA
Commons to ensure accurate and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit How to
Apply – Application Guide. If you encounter a system issue beyond your
control that threatens your ability to complete the submission process on-time,
you must follow the Dealing
with System Issues guidance. For assistance with application
submission, contact the Application Submission Contacts in Section VII.

Important
reminders:

All PD(s)/PI(s) must include their eRA Commons ID in
the Credential fieldof the Senior/Key Person Profile Component of the
SF424(R&R) Application Package. Failure to register in the Commons
and to include a valid PD/PI Commons ID in the credential field will prevent
the successful submission of an electronic application to NIH. See Section III of this FOA for information on
registration requirements.

The applicant organization must ensure that the DUNS
number it provides on the application is the same number used in the
organization’s profile in the eRA Commons and for the System for Award Management.
Additional information may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for
completeness and compliance with application instructions by the Center for
Scientific Review and responsiveness by components
of participating organizations, NIH. Applications that are incomplete, non-compliant
and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to
notify the NIMH Referral Office by email at nimhreferral@mail.nih.gov when the
application has been submitted. Please include the FOA number and title, PD/PI
name, and title of the application.

NIMH encourages the use of common data elements (CDEs) in
basic, clinical, and applied research, patient registries, and other human
subject research to facilitate broader and more effective use of data and
advance research across studies. CDEs are data elements that have been
identified and defined for use in multiple data sets across different studies.
Use of CDEs can facilitate data sharing and standardization to improve data
quality and enable data integration from multiple studies and sources,
including electronic health records. NIH ICs have identified CDEs for many
clinical domains (e.g., neurological disease), types of studies (e.g.
genome-wide association studies (GWAS)), types of outcomes (e.g.,
patient-reported outcomes), and patient registries (e.g., the Global Rare
Diseases Patient Registry and Data Repository). NIH has established a
"Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in
identifying NIH-supported CDEs when developing protocols, case report forms,
and other instruments for data collection. The Portal provides guidance about
and access to NIH-supported CDE initiatives and other tools and resources for the
appropriate use of CDEs and data standards in NIH-funded research.
Investigators are encouraged to consult the Portal and describe in their
applications any use they will make of NIH-supported CDEs in their projects.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in the policy.
Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process.

Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review
system.

A proposed Clinical Trial application may include study
design, methods, and intervention that are not by themselves innovative but
address important questions or unmet needs. Additionally, the results of the
clinical trial may indicate that further clinical development of the
intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact

Reviewers will provide an overall impact score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following review criteria and additional review criteria (as applicable for the
project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? Is the prior research that serves as
the key support for the proposed project rigorous? If the aims of the project
are achieved, how will scientific knowledge, technical capability, and/or
clinical practice be improved? How will successful completion of the aims
change the concepts, methods, technologies, treatments, services, or
preventative interventions that drive this field?

Does the research strategy describe a feasible
mechanism for scientific integration of research procedures and overall
managerial and administrative responsibilities across participating clinic
sites? Does the common research protocol address specify mechanisms for
cross-site coordination of clinical assessment, data collection, training and
supervision for the care team, fidelity monitoring, and database management to
assure reliability and quality control? Is the central data coordination and
statistical analysis support adequate for the overall project?

Is this clinical trial necessary to inform a change
in clinical practice or health care policy? Will the findings of this trial
advance scientific understanding about how to treat and manage people with OUDs
and co-occurring mental health disorders?

Does the application justify the practical effect of
the collaborative care intervention in terms of the estimated hypothesized
effect size (on the primary trial outcome), compared with already available
approaches? Does the application adequately address both (1) the empirical
basis for the anticipated effect size (e.g., citing appropriate data or
literature on collaborative care and/or MAT), and (2) the clinical
meaningfulness of the anticipated increment in effects compared to existing
approaches?

As appropriate, how well does the application seek to
answer research questions of secondary interest to NIH? For example:

Does the application address how treating mental health
conditions may improve outcomes for OUD?

Does the application describe the importance and implications of
an evidence-based approach to treatment sequencing for people with co-occurring
OUD and MH disorders?

If the approach is successful, is it scalable and sustainable,
and could it be implemented into practice given typically available resources
(e.g., trained, skilled providers), typical service structures (including
health care financing), and typical service use patterns?

Are the scientific rationale and need for a clinical
trial to test the proposed hypothesis or intervention well supported by
preliminary data, clinical and/or preclinical studies, or information in the
literature or knowledge of biological mechanisms? For trials focusing on
clinical or public health endpoints, is this clinical trial necessary for
testing the safety, efficacy or effectiveness of an intervention that could
lead to a change in clinical practice, community behaviors or health care
policy? For trials focusing on mechanistic, behavioral, physiological,
biochemical, or other biomedical endpoints, is this trial needed to advance
scientific understanding?

Investigator(s)

Are the PD(s)/PI(s), collaborators,
and other researchers well suited to the project? If Early Stage Investigators
or those in the early stages of independent careers, do they have appropriate
experience and training? If established, have they demonstrated an ongoing
record of accomplishments that have advanced their field(s)? If the project is
collaborative or multi-PD/PI, do the investigators have complementary and
integrated expertise; are their leadership approach, governance and
organizational structure appropriate for the project?

Are key personnel familiar with state and federal
regulations pertaining to MAT delivery? Are they familiar with commercial
insurance and Medicaid and Medicare benefits for MAT and collaborative care?

As appropriate, does the trial involve collaborations
and/or input from community practice partners/providers, consumers, and
relevant policy makers in a manner that informs the research and helps to
ensure the results will have immediate utility?

With regard to the proposed leadership
for the project, do the PD/PI(s) and key personnel have the expertise,
experience, and ability to organize, manage and implement the proposed clinical
trial and meet milestones and timelines? Do they have appropriate expertise in
study coordination, data management and statistics? For a multicenter trial, is
the organizational structure appropriate and does the application identify a
core of potential center investigators and staffing for a coordinating center?

Innovation

Does the application challenge and
seek to shift current research or clinical practice paradigms by utilizing
novel theoretical concepts, approaches or methodologies, instrumentation, or
interventions? Are the concepts, approaches or methodologies, instrumentation,
or interventions novel to one field of research or novel in a broad sense? Is a
refinement, improvement, or new application of theoretical concepts, approaches
or methodologies, instrumentation, or interventions proposed?

Does the application propose innovations to improve
care integration in terms of clinical workflow, treatment sequencing,
identification and management of high risk patients, or to improve care
pathways into collaborative care from other settings (e.g., the emergency
department)?

How well does the study incorporate innovative
research strategies and design/analytic elements (e.g., adaptive sequential
randomization, equipoise stratification) in order to enhance the study's
potential for yielding practice-relevant information?

Does the project adequately propose innovations in
workforce development, such as innovations in telehealth services, training and
supervision models, and or maximizing functions of non-physician providers with
prescription privileges (e.g., NPs, PAs, and psychologists) to inform future
prescribing guidelines and rules?

Does the design/research plan
include innovative elements, as appropriate, that enhance its sensitivity,
potential for information or potential to advance scientific knowledge or
clinical practice?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project? Have
the investigators included plans to address weaknesses in the rigor of prior
research that serves as the key support for the proposed project? Have the
investigators presented strategies to ensure a robust and unbiased approach, as
appropriate for the work proposed? Are potential problems, alternative
strategies, and benchmarks for success presented? If the project is in the
early stages of development, will the strategy establish feasibility and will
particularly risky aspects be managed? Have the investigators presented
adequate plans to address relevant biological variables, such as sex, for
studies in vertebrate animals or human subjects?

How well does the application describe the target
population and the settings where collaborative care is to be tested?

Does the application adequately discuss barriers and
facilitators associated with implementation, scalability, and sustainment of
collaborative care at the sites where the study will be conducted and how these
factors might affect generalizability of research findings to other primary
care practices?

Do the applicants take a deployment-focused model of
design and testing? That is, do studies take into account key characteristics
of the settings, providers, and intervention elements (e.g., training,
supervision, infrastructure, and capacity to pursue measurement-based care) and
factors related to implementation (reach, effectiveness, adoption, and
maintenance)? How pragmatic is the study design? Will procedures and
infrastructure unique to research (e.g., recruitment and follow-up strategies)
likely have minimal impact on clinical care and minimal impact on trial results?
Should the to-be-tested collaborative care model be effective, can it be
feasibly delivered outside of a clinical trial context? Specifically:

How representative are study populations and study settings to
community practice populations? Are relevant patient, provider, and
clinic-level factors assessed and manipulated? Will the approach generate
findings that can inform screening and treatment guidelines that may influence
how care is delivered to people with OUD and mental health problems?

Do applicants adequately leverage research practice partnerships,
networks, or other clinical infrastructure? If so, do they demonstrate
efficiencies or practice relevance by doing so? If not, have they provided
adequate for justification for why?

Are sites in areas of high need where OUD and co-occurring mental
health disorders are prevalent? Does the multi-site trial cover large
geographic areas where OUD mortality has risen particularly steeply?

Are projects equipped to utilize existing health care
billing/financing mechanisms whenever possible (e.g., use of CPT codes
99492/99493/99494, formerly G0502/G0503/G0504), and are projects designed to
inform how existing mechanisms can be used as part of a sustainable business
process, should clinics deliver collaborative care for people with OUDs and
mental health problems once the research concludes?

Is the study designed to differentiate outcomes associated with
study participation (e.g., patient completes follow-up assessments as reported
in a CONSORT), engagement with broad collaborative care services (e.g., patient
is responsive to care manager outreach calls), and individual treatment
elements delivered as part of collaborative care (e.g., patient takes
buprenorphine as prescribed and attends regular counseling sessions as part of
MAT)?

Is the design pragmatic such that it can control for and/or
minimize the impact of research personnel or procedures on study outcomes?

Will the selected comparison group(s) allow for
meaningful comparisons, given the robust evidence supporting widespread
implementation of collaborative care? Will findings be interpretable and inform
practice if the outcomes are positive, if outcomes are negative, and if there
is heterogeneity in the directionality of outcomes?

How adequately described is the collaborative care
model to be optimized and tested? Are all core elements of the model included
and consistent with acceptable practice? These are the 6 required core
elements:

1) A prepared primary care practice (e.g., routine
screening for indicated conditions; real-time availability and use of a disease
registry for measurement-based care and treat-to-target practices for a panel
of patients);

2) Care management services (in person and/or via
telehealth);

3) A behavioral health consultant with prescription
privileges, with collaborative care expertise and with MAT expertise (if the
behavioral health consultant does not have the prerequisite MAT expertise, applicants
must provide a plan for how that expertise will be obtained and provided to the
care team);

Is MAT appropriately described (e.g., to include the
induction, stabilization, and maintenance phases) and integrated with other
elements of collaborative care?

Does the project specify the patient outcomes that
will be the focus of treatment; provide detailed rationale for the choice of
outcomes; and describe valid and standardized methods for how those outcomes
will be measured? Are existing validated, standardized instruments of patient
outcomes, which are available for many mental disorders and for functioning,
utilized?

How well does the study design address whether the
intervention engages the services-oriented change mechanism(s) presumed to
underlie the effects of collaborative care (the mechanism(s) that accounts for
changes in clinical/ functional outcomes, changes in provider behavior, etc.)?
To what extent does the application include (1) a conceptual framework that
identifies the presumed mediator(s)/change mechanism(s); (2) plans for
assessing engagement of the target(s)/mechanism(s), including the specific
measures, the assessment schedule, and the justification for the assessment
strategy ; and (3) an appropriate analytic strategy a to examine whether the
collaborative care engages the presumed target(s)/mechanism(s) and whether
collaborative care-induced changes in the mechanism(s) are associated with
benefit in the primary endpoints (i.e., mediation)?

How well does the application answer questions of
secondary interest to NIH such as whether treating mental health conditions
will improve OUD-related outcomes?

Does the application adequately address the
following, if applicable

Study
Design

Is the study design justified and appropriate to address
primary and secondary outcome variable(s)/endpoints that will be clear,
informative and relevant to the hypothesis being tested? Is the scientific
rationale/premise of the study based on previously well-designed preclinical
and/or clinical research? Given the methods used to assign participants and
deliver interventions, is the study design adequately powered to answer the
research question(s), test the proposed hypothesis/hypotheses, and provide
interpretable results? Is the trial appropriately designed to conduct the
research efficiently? Are the study populations (size, gender, age, demographic
group), proposed intervention arms/dose, and duration of the trial, appropriate
and well justified?

Are potential ethical issues adequately addressed? Is
the process for obtaining informed consent or assent appropriate? Is the
eligible population available? Are the plans for recruitment outreach,
enrollment, retention, handling dropouts, missed visits, and losses to
follow-up appropriate to ensure robust data collection? Are the planned
recruitment timelines feasible and is the plan to monitor accrual adequate? Has
the need for randomization (or not), masking (if appropriate), controls, and
inclusion/exclusion criteria been addressed? Are differences addressed, if
applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and
monitor adherence to, the trial protocol and data collection or distribution
guidelines appropriate? Is there a plan to obtain required study agent(s)? Does
the application propose to use existing available resources, as applicable?

Data
Management and Statistical Analysis

Are planned analyses and
statistical approach appropriate for the proposed study design and methods used
to assign participants and deliver interventions? Are the procedures for data
management and quality control of data adequate at clinical site(s) or at
center laboratories, as applicable? Have the methods for standardization of
procedures for data management to assess the effect of the intervention and
quality control been addressed? Is there a plan to complete data analysis
within the proposed period of the award?

If the project involves human
subjects and/or NIH-defined clinical research, are the plans to address

1) the protection of human subjects
from research risks, and

2) inclusion (or exclusion) of individuals on the
basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion
of individuals of all ages (including children and older adults), justified in
terms of the scientific goals and research strategy proposed?

Are protections for high risk
patients in this research context assessed against an appropriate standard of
care that is not artificially high for the target population? Will study
procedures to manage risk contaminate care as usual or the intervention(s)
being tested? That is, have applicants appropriately balanced the need to
protect human subjects with the need to conduct trials that are highly
generalizable to the practice settings.

Environment

Will the scientific environment in
which the work will be done contribute to the probability of success? Are the
institutional support, equipment and other physical resources available to the
investigators adequate for the project proposed? Will the project benefit from
unique features of the scientific environment, subject populations, or
collaborative arrangements?

As appropriate, are the plans achievable for
establishing necessary agreements with all partners (e.g., single IRB) in a
timely manner?

If proposed, are the administrative, data
coordinating, enrollment and laboratory/testing centers, appropriate for the
trial proposed?

Does the application adequately address the
capability and ability to conduct the trial at the proposed site(s) or centers?
Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the
application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there
evidence of the ability of the individual site or center to: (1) enroll the
proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in
an accurate and timely fashion; and, (4) operate within the proposed organizational
structure?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact score, but will not give
separate scores for these items.

Collaboration

Are sufficient and feasible mechanisms in place to
ensure collaboration across sites to achieve scientific integration of research
procedures, overall managerial and administrative responsibilities, appropriate
quality control and reliability assurance, and planning for data management,
analysis and reporting of results? Are there adequate plans for shared decision
making among PDs/PIs with regard to personnel, clinical decisions, changes in
study protocol, and authorship?

Is the process for establishing and convening a
Steering Committee adequate?

Study Timelines

Are milestones achievable and appropriate for the
trial? Are milestones being evaluated regularly?

Is the study timeline described in detail, taking
into account start-up activities, the anticipated rate of enrollment, and
planned follow-up assessment? Is the projected timeline feasible and well
justified? Does the project incorporate efficiencies and utilize existing
resources (e.g., CTSAs, practice-based research networks, electronic medical
records, administrative database, or patient registries) to increase the
efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions
discussed (e.g., strategies that can be implemented in the event of enrollment
shortfalls)?

Protections for Human Subjects

For research that involves human
subjects but does not involve one of the categories of research that are exempt
under 45 CFR Part 46, the committee will evaluate the justification for
involvement of human subjects and the proposed protections from research risk
relating to their participation according to the following five review
criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3)
potential benefits to the subjects and others, 4) importance of the knowledge
to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human
subjects and meets the criteria for one or more of the categories of research
that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the
justification for the exemption, 2) human subjects involvement and
characteristics, and 3) sources of materials. For additional information on
review of the Human Subjects section, please refer to the Guidelines for the Review of Human
Subjects.

Inclusion of Women, Minorities, and Individuals Across
the Lifespan

When the proposed project involves
human subjects and/or NIH-defined clinical research, the committee will
evaluate the proposed plans for the inclusion (or exclusion) of individuals on
the basis of sex/gender, race, and ethnicity, as well as the inclusion (or
exclusion) of individuals of all ages (including children and older adults) to
determine if it is justified in terms of the scientific goals and research
strategy proposed. For additional information on review of the Inclusion
section, please refer to the Guidelines for the Review of Inclusion
in Clinical Research.

Vertebrate Animals

The committee will evaluate the
involvement of live vertebrate animals as part of the scientific assessment
according to the following criteria: (1) description of proposed procedures
involving animals, including species, strains, ages, sex, and total number to
be used; (2) justifications for the use of animals versus alternative models
and for the appropriateness of the species proposed; (3) interventions to
minimize discomfort, distress, pain and injury; and (4) justification for
euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia
of Animals. Reviewers will assess the use of chimpanzees as they would any
other application proposing the use of vertebrate animals. For additional
information on review of the Vertebrate Animals section, please refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether
materials or procedures proposed are potentially hazardous to research
personnel and/or the environment, and if needed, determine whether adequate
protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact score.

Applications from Foreign
Organizations

Not Applicable

Select Agent Research

Reviewers will assess the
information provided in this section of the application, including 1) the Select
Agent(s) to be used in the proposed research, 2) the registration status of all
entities where Select Agent(s) will be used, 3) the procedures that will be
used to monitor possession use and transfer of Select Agent(s), and 4) plans
for appropriate biosafety, biocontainment, and security of the Select Agent(s).

For projects involving key biological and/or chemical resources,
reviewers will comment on the brief plans proposed for identifying and ensuring
the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the
budget and the requested period of support are fully justified and reasonable
in relation to the proposed research.

Specific to this FOA:

How likely is it that the plans for cost matching
will be adequate?

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by NIMH, in
accordance with NIH peer
review policy and procedures, using the stated review
criteria. Assignment to a Scientific Review Group will be shown in the eRA
Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact
score.

Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in
response to this FOA.

Applications will be assigned on the basis of established
PHS referral guidelines to the appropriate NIH Institute or Center. Applications
will compete for available funds with all other recommended applications submitted
in response to this FOA. Following initial peer review, recommended applications
will receive a second level of review by the appropriate national Advisory
Council or Board. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as determined
by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons. Refer to Part 1 for dates for peer review, advisory council
review, and earliest start date.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA)
will be provided to the applicant organization for successful applications. The
NoA signed by the grants management officer is the authorizing document and
will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described
in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be
subject to terms and conditions found on the Award
Conditions and Information for NIH Grants website. This includes any
recent legislation and policy applicable to awards that is highlighted on this
website.

Individual awards are based on the application submitted to,
and as approved by, the NIH and are subject to the IC-specific terms and
conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more
clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the
"responsible party" must register and submit results information for
certain “applicable clinical trials” on the ClinicalTrials.gov Protocol
Registration and Results System Information Website (https://register.clinicaltrials.gov).
NIH expects registration of all trials whether required under the law or not.
For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/

Institutional Review Board or Independent Ethics Committee
Approval: Grantee institutions must ensure that the application as well as all
protocols are reviewed by their IRB or IEC. To help ensure the safety of
participants enrolled in NIH-funded studies, the awardee must provide NIH
copies of documents related to all major changes in the status of ongoing
protocols. Data and Safety Monitoring Requirements: The NIH policy for data
and safety monitoring requires oversight and monitoring of all NIH-conducted or
-supported human biomedical and behavioral intervention studies (clinical
trials) to ensure the safety of participants and the validity and integrity of
the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption
Requirements: Consistent with federal regulations, clinical research projects
involving the use of investigational therapeutics, vaccines, or other medical
interventions (including licensed products and devices for a purpose other than
that for which they were licensed) in humans under a research protocol must be
performed under a Food and Drug Administration (FDA) investigational new drug
(IND) or investigational device exemption (IDE).

Special award condition specific to this FOA: A grantee from
a for-profit organization funded under this announcement must match funds or
provide documented in-kind contributions at a rate of not less than 50% of the
total-Federally awarded amount, as stipulated by Public Law 115-141, the
Consolidated Appropriations Act of 2018. See 45 CFR 75.306 for additional
details. Matching funds must be non-Federal funds set aside for this project
and are available from the source(s) identified in the application, as
committed to by the recipient. Cost matching will be evaluated by the
awarding office to ensure that this requirement is being met. Compliance with
the matching requirement must be verified on an annual basis and must be
documented in the annual and final FFR.

Recipients of federal financial
assistance (FFA) from HHS must administer their programs in compliance with
federal civil rights law. This means that recipients of HHS funds must ensure
equal access to their programs without regard to a person’s race, color,
national origin, disability, age and, in some circumstances, sex and religion.
This includes ensuring your programs are accessible to persons with limited
English proficiency. HHS recognizes that research projects are often limited
in scope for many reasons that are nondiscriminatory, such as the principal
investigator’s scientific interest, funding limitations, recruitment
requirements, and other considerations. Thus, criteria in research protocols
that target or exclude certain populations are warranted where
nondiscriminatory justifications establish that such criteria are appropriate
with respect to the health or safety of the subjects, the scientific study
design, or the purpose of the research.

In accordance with the statutory provisions contained in
Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal
Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal
Awardee Performance and Integrity Information System (FAPIIS) requirements.
FAPIIS requires Federal award making officials to review and consider information
about an applicant in the designated integrity and performance system
(currently FAPIIS) prior to making an award. An applicant, at its option, may
review information in the designated integrity and performance systems
accessible through FAPIIS and comment on any information about itself that a
Federal agency previously entered and is currently in FAPIIS. The Federal
awarding agency will consider any comments by the applicant, in addition to
other information in FAPIIS, in making a judgement about the applicant’s
integrity, business ethics, and record of performance under Federal awards when
completing the review of risk posed by applicants as described in 45 CFR Part
75.205 “Federal awarding agency review of risk posed by applicants.” This
provision will apply to all NIH grants and cooperative agreements except
fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (DHHS)
grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH
grant administration policies.

The administrative and funding instrument used for this program will be the
cooperative agreement, an "assistance" mechanism (rather than an
"acquisition" mechanism), in which substantial NIH programmatic
involvement with the awardees is anticipated during the performance of the activities.
Under the cooperative agreement, the NIH purpose is to support and stimulate
the recipients' activities by involvement in and otherwise working jointly with
the award recipients in a partnership role; it is not to assume direction,
prime responsibility, or a dominant role in the activities. Consistent with
this concept, the dominant role and prime responsibility resides with the
awardees for the project as a whole, although specific tasks and activities may
be shared among the awardees and the NIH as defined below.

The
PD(s)/PI(s) will have the primary responsibility for:

Define the details of the project within the guidelines of this
FOA.

Assume responsibility and accountability to the applicant
organization and to NIH for performance and proper conduct of all research in
accordance with the Terms and Conditions of Award.

Accept close coordination, cooperation, and participation of NIH
program staff in the scientific, technical, and administrative management of
the grant.

Provide milestones and cost for the grant to NIH program staff as
requested (usually at the onset of the award and annually thereafter, but also
at other times as requested).

Chair and coordinate the activities of the Steering Committee.
The Chair is responsible for preparing meeting agendas, scheduling and chairing
meetings, and preparing concise minutes which will be delivered to Steering
Committee members within 2 weeks of the meeting. Virtual meetings are
appropriate.

Serve as a member of the Steering Committee and fulfill related
duties outlined below in Areas of Joint Responsibility; inform the NIMH Program
Official of all major interactions with other members of the Steering
Committee.

Adhere to NIMH policies regarding intellectual property and other
policies that might be established during the course of this project activity.
Awardees will retain custody of and have primary rights to the data and
software developed under these awards, subject to Government rights of access
consistent with current DHHS, PHS, and NIH policies.

The PI will have responsibility for depositing all data collected
under this award, including de-identified patient-level data, in the NIMH Data
Archive (see NDA; https://data-archive.nimh.nih.gov/),
consistent with achieving the goals of the program. All data collected are
expected to be deposited into NDA every 12 months, as appropriate and
consistent with achieving the goals of the program.

Publication or oral presentation of work done under this
agreement will require appropriate acknowledgment of NIMH support, including
the assigned cooperative agreement award number.

Share data and resources according to the data release and
resource sharing policies developed for and by this project as appropriate and
consistent with achieving the goals of the project.

Fully disclose algorithms and software source code and analytic
approaches to all site clinics and on a publicly accessible site (e.g., github)

Not disclose confidential or protected information obtained from
sites or patients.

Submit data for quality assessment and/or validation in any
manner specified by the Steering Committee and/or the NIMH program staff to
ensure scientific rigor.

Accept and implement the common guidelines and procedures
approved by the Steering Committee and NIMH.

Coordinate and collaborate with awardees of this and other HEAL
initiatives to improve dissemination of important findings, identify and
analyze common data elements (especially for low base rate events) to assist
with decision making and improve overall public health impact of this trans-NIH
HEAL initiative.

Awardees will retain custody of and have primary rights to the
data and software developed under these awards, subject to Government rights of
access consistent with current DHHS, PHS, and NIH policies.

NIH
staff have substantial programmatic involvement that is above and beyond the
normal stewardship role in awards, as described below:

An NIMH Program Official will be responsible for the normal
scientific and programmatic stewardship of the award, including programmatic
monitoring and assistance in the coordination of the overall project and
implementation of the data and research resource sharing plans, and will be
named in the award notice.

The NIMH Program Official may attend and participate in steering
committee meetings as a non-voting member.

The NIMH reserves the right to terminate or curtail the clinical
trial (or an individual component of the award) in the event of inadequate
progress, data reporting, insufficient use of this resource, or safety issues.

The NIMH Program Officer will interact with the PD(s)/PI(s) on a
regular basis to monitor progress. Monitoring may include: regular
communication with the PI and his/her staff, periodic site visits for
discussion with the awardee research team, observation of field data collection
and management techniques, fiscal reviews, and other relevant stewardship
matters.

The NIMH Program Officer may also identify additional extramural
staff from NIMH and other participating organizations that have appropriate
experience and expertise to collaborate with the study team to review study
designs and methods, participation in study analyses, and review of scientific
reports and articles.

In addition to the Program Official, an NIH Project Scientist(s)
may be named to the Steering Committee as a voting member. The role of the NIMH
Project Scientist(s) is one of substantial involvement above and beyond the
normal program stewardship role of a Program Official. The participation of the
Project Scientist(s) is intended to assist the Steering Committee in its
efforts to ensure that the broad scientific goals of NIH are reflected in the
final design, implementation, and reporting of results of the trial.

The role of the NIH Project Scientist(s) is to assist,
participate in deliberations, and facilitate discussion, but not to direct
activities. This level of staff involvement does not alter the awardee’s
dominant role and prime authority in conducting the activities of the trial.
The NIH Project Scientist(s) may cooperate with the awardee as author or
co-author of resulting publications in accordance with publication policies
developed by the Steering Committee. Publications involving NIH staff must
follow NIH publication policies.

Areas
of Joint Responsibility include:

A governing Steering Committee will be established to assist in
ensuring that the aims of the trial are achieved and milestones are met. The
Steering Committee will be composed of the PD(s)/PI(s); key personnel; the NIH
Project Scientist(s); senior members of the local treatment team or clinic leadership;
and additional members that reflect the diversity of mental health and
addiction stakeholders, such as patients and relatives, clinicians, health
system administrators, and health care policy makers from local, state, or
federal government. Experts in learning health care, measurement-based
treatment, health information technology, health informatics, computational
modeling, bioethics, and other areas may also be included, as appropriate.

Steering Committee members will meet periodically, but not fewer
than twice per year, to plan research activities, review study progress, and
establish priorities, policies, and procedures. Each member will have one vote
in any decision to be made by the Steering Committee with respect to study
policies and procedures. The NIH Project Scientist(s) will be a voting
member of the Steering Committee. Adoption of policies and procedures will
require a majority vote.

Any disagreements that may arise in scientific or
programmatic matters (within the scope of the award) between award recipients
and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel
composed of three members will be convened. It will have three members: a
designee of the Steering Committee chosen without NIH staff voting, one NIH
designee, and a third designee with expertise in the relevant area who is
chosen by the other two; in the case of individual disagreement, the first member
may be chosen by the individual awardee. This special dispute resolution
procedure does not alter the awardee's right to appeal an adverse action that
is otherwise appealable in accordance with PHS regulation 42 CFR Part 50,
Subpart D and DHHS regulation 45 CFR Part 16.

A final Research Performance Progress Report (F-RPPR), invention statement, and the expenditure data portion of the Federal Financial Report, including Federal and non-Federal share for cost matching, are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH
Grants Policy Statement for additional information on this reporting
requirement.

In accordance with the regulatory requirements provided at
45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have
currently active Federal grants, cooperative agreements, and procurement
contracts from all Federal awarding agencies with a cumulative total value
greater than $10,000,000 for any period of time during the period of
performance of a Federal award, must report and maintain the currency of
information reported in the System for Award Management (SAM) about civil,
criminal, and administrative proceedings in connection with the award or performance
of a Federal award that reached final disposition within the most recent
five-year period. The recipient must also make semiannual disclosures
regarding such proceedings. Proceedings information will be made publicly
available in the designated integrity and performance system (currently
FAPIIS). This is a statutory requirement under section 872 of Public Law
110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public
Law 111-212, all information posted in the designated integrity and performance
system on or after April 15, 2011, except past performance reviews required for
Federal procurement contracts, will be publicly available. Full reporting
requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award
Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.